Analysis of transgenic mice expressing human parvovirus non-stractual (NS1) protein
| Project/Area Number |
12470067
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Virology
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAMURA Kazuo Tohoku Univ. Graduate Sch. of Med., Dept. of Microbiol. & Immunol., Professor, 大学院・医学系研究科, 教授 (20117360)
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| Co-Investigator(Kenkyū-buntansha) |
ISHII Naoto Tohoku Univ. Graduate Sch. of Med., Dept. of Microbiol. & Immunol., Research Associate, 大学院・医学系研究科, 助手 (60291267)
ASAO Hironobu Tohoku Univ. Graduate Sch. of Med., Dept. of Microbiol. & Immunol., Associate Professor, 大学院・医学系研究科, 助教授 (80250744)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2000: ¥7,600,000 (Direct Cost: ¥7,600,000)
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| Keywords | Human parvovirus B19 / transgenic mice / NS1 / non-immune hydrops fetalis / apoptosis / G2 arrest |
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| Research Abstract |
Human parvovirus B19 is the cause of several distinct clinical syndromes. The most common is erythema infectiosum (fifth disease), a febrile exanthem occurring primarily in children. Recent studies have shown that parvovirus B19 can cause acute arthritis and occasionally a chronic arthropathy, both in children and adults. In this study, we generated transgenic mice expressing a viral non-structural (NS1) protein and analyzed its functional importance. Most of the transgenic mice died at the embryonic stage, some of which developed hydropic changes caused by severe anaemia at embryonic day 15.5 (E15.5). Histological examination of embryos at E15.5 showed significantly fewer erythropoietic islands in the liver parenchyma, whereas their hearts showed no abnormal signs, such as cardiomegaly and apoptotic cells. The NS1-transgenic mouse lines established here provide an animal model for human NIHF (non-immune hydrops fetalis) and suggest that NS1 plays a crucial role in the adverse outcome
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associated with intrauterine B19 infection in humans. Furthermore, we demonstrate that erythroblastoid UT7/Epo cells infected with B19 virus fall into growth arrest with 4N DNA, indicating G(2)/M arrest. These B19 virus-infected cells displayed accumulation of cyclin A, cyclin B1, and phosphorylated cdc2 and were accompanied by an up-regulation in the kinase activity of the cdc2-cyclin B1 complex, similar to that in cells treated with the mitotic inhibitor. However, degradation of nuclear lamina and phosphorylation of histone H3 and H1 were not seen in B19 virus-infected cells, indicating that the infected cells do not enter the M phase. Accumulation of cyclin B1 was persistently localized in the cytoplasm, but not in the nucleus, suggesting that B19 virus infection of erythroid cells raises suppression of nuclear import of cyclin B1, resulting in cell cycle arrest at the G(2) phase. The B19 virus-induced G(2)/M arrest may be the critical event hi the damage of erythroid progenitor cells seen in patients with B19 virus infection. Less
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Report
(3 results)
Research Products
(10 results)
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[Publications] Chisaka, H., Morita, E., Murata, K., Ishii, N., Yaegashi, N., Okamura, K. and Sugamura, K.: "A transgenic mouse model for non-immune hydrops fetalis induced by the NS1 gene of human parvovirus B19."J. General Virology. Vol. 83. 273-281 (2002)
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Related Report
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[Publications] Morita, E., Tada, K., Chisaka, H., Asao, H., Sato, H., Yaegashi, N. and Sugamura, K.: "Human parvovirus B19 induces cell cycle arrest at G2 phase with accumulation of mitotic cyclins."J. Virology. Vol. 75, 16. 7555-7563 (2001)
Description
「研究成果報告書概要(欧文)」より
Related Report
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